1. Field of the Invention
The present invention relates to an apparatus for non-invasive, real-time, continuous and/or discretely monitoring of cerebral venous oxygenation and a method for continuously and/or discretely monitoring tissue oxygenation including venous oxygenation.
More particularly, the present invention relates to an optoacoustic apparatus including one or more nanosecond pulsed laser, a probe including a sensitive acoustic transducer located in a head of the probe, a fiber-optic delivery system connected to each laser and terminating in the head of the probe, and hardware and software for converting a received acoustic signal into a measure of tissue oxygenation including cerebral venous oxygenation. The present invention also relates to methods for monitoring tissue oxygenation and for making the apparatus of this invention. The present invention is especially well suited for non-invasive monitoring of tissue sites that otherwise would be hard to monitor even with invasive monitoring apparatuses and methods.
2. Description of the Related Art
Over the past fifteen years, compelling clinical evidence has accumulated to suggest that monitoring cerebral oxygenation can detect otherwise unrecognized cerebral ischemia and be used to guide therapeutic interventions. Although randomized clinical trials do not yet demonstrate that interventions based on cerebral oxygenation monitoring can influence outcome, abundant evidence illustrates the association between cerebral hypoxia and worse outcome in such diverse situations as traumatic brain injury and cardiac surgery using cardiopulmonary bypass. In such situations, unlike circumstances in healthy humans, the adequacy of cerebral oxygen delivery (the product of cerebral blood flow and arterial oxygen content) cannot be inferred from measurements of systemic blood pressure and arterial oxygenation because cerebral blood flow is inadequate to satisfy cerebral metabolic demand. To date, the two primary methods used to monitor brain oxygenation are invasivexe2x80x94one requires percutaneous insertion of a catheter into the jugular bulb to continuously measure cerebral venous oxygenation and the other requires insertion of a probe through the skull into the brain parenchyma to measure tissue PO2. Jugular venous bulb monitoring is based on the following equation:
CjvO2=CaO2xe2x88x92CMRO2/CBFxe2x80x83xe2x80x83(1)
where CjvO2 represents jugular venous bulb oxygenation content; CaO2 represents arterial oxygen content; CMRO2 represents the cerebral metabolic rate for oxygen; and CBF represents cerebral blood flow [1]. Because oxygen content is linearly related to hemoglobin oxygen saturation at a constant hemoglobin concentration, SjvO2 can be measured or monitored as a surrogate for jugular venous oxygen content.
Jugular venous monitoring provides a global assessment of brain oxygenation, but requires frequent recalibration and is invasive, thereby both introducing the complications of catheter insertion and also delaying the initiation of brain oxygenation monitoring until a patient has been acutely stabilized. Nevertheless, jugular venous bulb measurements have been used in extensive clinical investigations in head-injured patients [2-9] and during cardiac surgery [10-16] and have proven clinically useful in patients who have traumatic brain injury [4, 6] and in patients undergoing cardiopulmonary bypass [10, 17].
Most importantly, single episodes ofjugular venous desaturation have been associated with worse outcome after traumatic brain injury [6] and jugular venous desaturation during rewarming after hypothermic cardiopulmonary bypass has been associated with worse cognitive performance after cardiopulmonary bypass [18]. Clinical protocols have been developed that initiate interventions such as changing blood pressure or PaCO2 in response to decreasing SjvO2[4, 6].
More recently, brain tissue PO2 monitoring has been introduced for the management of patients with traumatic brain injury [19]. In patients with traumatic brain injury, brain tissue PO2 correlates highly with outcome [19]. However, although brain tissue PO2 monitoring provides a precise regional measurement of tissue oxygenation, it provides no information about inadequate tissue oxygenation in remote sites.
Near-infrared spectroscopy, a third, noninvasive method of monitoring cerebral blood oxygenation, utilizes differences in optical absorption coefficients of oxy- and deoxyhemoglobin [20, 21]. Two wavelengths of the NIR spectral range are usually used in the optical oximeters. One wavelength is shorter and the other is longer than 805 nm (isosbestic point). The technique is promising, but has yet to be satisfactorily calibrated to provide quantitative measurement of cerebral venous oxygenation [22, 23] at least in part because techniques have not been devised to distinguish venous from arterial blood [24].
Moreover, unlike the remarkable success of pulse oximetry for monitoring of systemic arterial hemoglobin saturation, the development of near-infrared monitoring of brain oxygenation has been slowed by the difficulty posed by measuring or estimating the pathlength of scattered light through biologic media [25]. Strong light scattering in tissues presents a great obstacle to quantitative measurement of cerebral blood oxygenation.
Encouraging reports of the use of near-infrared spectroscopy during carotid endarterectomy [26] and cardiac surgery [27] must be balanced against the fact that current technology is qualitative and can be used only as a trend monitor rather than as accurate measurement technique. As a consequence, the technique has yet to be incorporated into routine clinical practice. However, the technology continues to improve as investigators continue to develop more accurate methods of quantifying the signal [28, 29A].
Recently, the method of near-infra-red spectroscopy at two wavelengths coinciding with maxima of oxy and deoxy hemoglobin in microcirculation network of tumors, angiogenesis, was shown useful in differentiating malignant and benign tumors [29B]. However, resolution of pure optical imaging method is insufficient to determine exact dimensions, shape and location of tumors.
Therefore, despite major advances in understanding the physiology of the blood circulation in patients, including patients at high risk for neurologic injury, clinical monitoring of tissue oxygenation including brain oxygenation remains invasive and relatively expensive. Moreover, these procedures generally cannot easily be initiated until a patient is stabilized or until diagnostic tests such as computed tomography or magnetic resonance imaging are completed. Furthermore, these procedures often cannot be initiated until the patient is transferred to the operating suite or intensive care unit. Thus, there is a need in the art for a non-invasive, real-time, continuous and/or discrete monitoring of tissue oxygenation including cerebral venous oxygenation.
The present invention provides an optoacoustic apparatus including one or more short duration pulsed lasers (preferably the duration is in the nanosecond or shorter duration) and a fiber-optic delivery system including a plurality of optical fibers, where the fibers, at their proximal ends, are optically connected to an output of the laser(s) and terminate in a distal face of an irradiation probe. The apparatus also includes an acoustic probe having a pressure sensing device such as a piezoelectric transducer mounted in a distal face of the acoustic probe. The transducer is connected via a cable which exits from a proximal end of the acoustic probe to a processing unit that converts a transducer output signal into a measure of blood oxygenation of a target tissue. The output signal can include information about venous and/or arterial blood oxygenation depending on the area of irradiation and area of acoustic detection.
The present invention provides an optoacoustic apparatus including one or more short duration pulsed lasers (preferably the duration is in the nanosecond or shorter duration) and a fiber-optic delivery system including a plurality of optical fibers, where the fibers, at their proximal ends, are optically connected to an output of the laser(s). The apparatus also includes a probe having a pressure sensing device such as a piezoelectric transducer mounted in a distal face of a distal end of the probe and a proximal end adapted to receive the fiber-optics delivery system. The optical fibers terminate at or in the distal face of the probe and are preferably distributed around or surround the transducer. The transducer is connected via a cable which exits from the proximal end of the probe to a processing unit that converts the transducer output signal into a measure of blood oxygenation of a target tissue site such as Superior Sagittal Sinus. Again, the output signal can include information about venous and/or arterial blood oxygenation depending on the area of irradiation and area of acoustic detection.
The present invention also provides an optoacoustic apparatus including one or more short duration pulsed lasers and a fiber-optic delivery system including a plurality of optical fibers, where the fibers, at their proximal ends, are optically connected to an output of the laser(s) and to an irradiation probe at its distal end where the fibers terminate in a face of the irradiation probe. The apparatus also includes an acoustic probe having a pressure sensing device such as a piezoelectric transducer mounted in a front face of a distal end of the probe. The transducer is connected via a cable which exits from a proximal end of the acoustic probe to a processing unit that converts the transducer output into a measure of blood oxygenation of a target tissue site such as Superior Sagittal Sinus
The present invention also provides an acoustic probe including a housing having a proximal end and a distal end. The probe also includes a distal face in the distal end of the probe, which includes a pressure sensing apparatus such as a piezoelectric transducer mounted thereon or therein and connected to an output cable that exits from the proximal end of the probe, where the distal face is adapted to be placed in close proximity to or in contact with a target tissue site and to receive an acoustic signal therefrom.
The present invention also provides an irradiation probe including a housing having a proximal end and a distal end. The irradiation probe also includes an optical fiber cable including a plurality of optical fibers entering the probe at its proximal end. The fibers terminate at or in a distal face of the distal end of the probe. The optical fibers act as light conduits for laser light energy when connected to a pulsed laser. The irradiation probe is designed to be placed in close proximity to or in contact with a target tissue site to permit pulsed laser light to impinge on the site which is thermalized by tissue in the site resulting in pressure waves or an acoustic signal which are/is detected by the acoustic probe. The detected signal is then related to tissue blood oxygenationxe2x80x94blood oxygen content within the target tissue.
The present invention also provides a probe including a housing having a proximal end and a distal end. The probe also includes a distal face in the distal end of the probe, which includes a pressure sensing apparatus such as a piezoelectric transducer mounted thereon or therein and connected to an output cable that exits from the proximal end of the probe. The probe also includes an optical fiber cable including a plurality of optical fibers entering the probe at its proximal end. The fibers terminate at or in the front face of the probe. The optical fibers act as light conduits for laser light energy when connected to a pulsed laser. The probe is designed to permit pulsed laser light to impinge on a body site which is thermalized by a target tissue site resulting in formation of pressure waves or an acoustic signal which are/is detected by the pressure sensing apparatus. The detected signal is then related to tissue blood oxygenationxe2x80x94blood oxygen content within the target tissue, venous and/or arterial.
The present invention further provides a method for measuring blood oxygenation including the step of directing radiation from a laser via optical fibers terminating in a distal face of a probe of present invention, where the distal face is in optical and acoustic contact with a target tissue site of an animal including a human. The light leaves the probe face and enters the target tissue site causing the production of an acoustic signal in the target tissue site. The acoustic signal is thought to result from thermalization of light energy. The acoustic signal is received by a pressure sensing apparatus such as a transducer mounted on or in the distal or front face of the probe producing a output signal. The signal is then transmitted to a processing unit which converts the signal into a measure of blood oxygenation. The method can also include displaying the measurement on a display device. Preferably, the radiation is pulsed and particularly, the radiation is pulsed in a nanosecond time frame.
The present invention also provides a method for monitoring blood oxygenation in a tissue or a blood vessel including irradiating the tissue or the blood vessel with at least one laser pulse. The pulse causes the generation of an acoustic signal corresponding to a distribution of thermoelastic optoacoustic pressure profiles of the absorbed laser energy in the tissue or vessel. The signal is detected with at least one acoustic detector in a time-resolved manner. The detector signal is then analyzing and the temporal profiles and/or signal amplitudes of the optoacoustic waves with a related to the oxygenation level of hemoglobin in blood within the tissue or vessel. The method can include laser light at a or single wavelength or multiple wavelengths depending on properties or factors such as the location of the tissue or vessel, the amount of other body structures to be penetrated (bone, thick tissue, etc.), blood concentration in the tissue or vessel or other properties or factors.
The present invention also provides a system for carrying out the above-states method including a pulsed laser system or other system capable of generating short optical pulses to provide irradiation of a tissue or vessel. The systems also includes a light communication system such as a fiber-optic system or articulated mirror arm optical system for delivering laser pulses to the tissue or vessel and an acoustic detection systems including at least one acoustic transducer for pressure profile detection with sufficient sensitivity, temporal resolution, and bandwidth so that thermoelastic optoacoustic pressure profiles of the absorbed laser energy in the tissue or vessel can be detected. The system also includes an adjustable holder for the light delivery system and the acoustic transducer(s) to provide appropriate irradiation conditions and acoustic contact between the investigated tissue or vessel and the acoustic transducer(s) and an electronic system for signal recording and processing. The system can also include a digital processing or computer system that converts a signal from the acoustic detection system into a measure of blood oxygenation in the tissue or vessel.
The present invention still further provides a method for relating an acoustic signal to an oxygenation index for blood in a target tissue site of an animal, including a human.